Donor Leukocytes:
A Transfusion Risk May Remain Even After Leukoreduction
The presence of viable donor leukocytes in donated blood has long been recognized as a source of risk for recipients. Transfusion-associated graft-versus-host disease (TA-GVHD) caused by proliferation of donor T-cells in the recipient may carry a mortality rate as high as 84%. In addition, cytokines released by leukocytes during unit storage can cause febrile non-hemolytic transfusion reactions (FNHTR) [45]. Finally, leukocytes can also harbor latent viruses such as CMV and HTLV [46].
Current Safeguards
Gamma irradiation is a common treatment option used to inactivate donor leukocytes and reduce the incidence of TA-GVHD. Leukoreduction is another standard tool for reducing risk to recipients, and leukofiltered units contain a much reduced number of white cells. However, any residual leukocytes may still be capable of proliferation, leading to theories that gamma irradiation is still indicated for blood products intended for patients at risk of GVHD [47].
Benefits of the INTERCEPT Blood System
During the INTERCEPT Blood System pathogen inactivation process, leukocytes are also inactivated — preventing both leukocyte replication and cytokine production.
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| |
Leuko-reduction |
Gamma-
irradiation |
INTERCEPT
Blood System |
| Mechanism |
Filters out leukocytes |
Irradiation damages the genetic material of pathogens |
Amotosalen molecule crosslinks the genetic material of both leukocytes and pathogens that may be present and inhibits cellular function and replication |
| Effectiveness |
Residual leukocytes may still be present after leukoreduction |
Introduces one nucleic acid strand break every ~37,000 base pairs
|
Introduces a nucleic acid crosslink every ~83-89 base pairs* |
| Post-Transfusion Complications |
Live donor leukocytes can cause GvHD and FNHTR |
Irradiated leukocytes are still able to produce cytokines [48]; FNHTR may still occur
|
Inactivated leukocytes reduce the probability of both GvHD and FNHTR |
| Additional Information |
Does not address the problem of cell-free pathogens; does not alter cytokine levels at time of filtration; CMV transmission still possible in immuno-
compromised patients [49] |
Does not address the problem of pathogens; gamma doses used to inactivate leukocytes are not intended to be virucidal, and CMV may be recovered from infected host cells [50]
|
Also effective against a broad spectrum of pathogens, including cell-associated CMV |
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* Approved product claims – see leukocyte inactivation information in technical data sheets for INTERCEPT Platelets and INTERCEPT Plasma.
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